The Clinical Component of the University of Alabama at Birmingham (UAB) Autoimmunity Center of Excellence (ACE) will be directed by Drs. Larry Moreland and Joseph Shanahan. The Clinical Director will serve as the Clinical Representative to the Steering Committee and will coordinate the effort of the UAB ACE with the national network. Dr. Moreland, in his roles as Director of the Arthritis Clinical Intervention Program (ACIP) and the UAB Pittman General Clinical Research Center (GCRC), will guide the infrastructure for clinical trials for UAB and ACE projects. The UAB ACIP has in place the infrastructure for regulatory and financial oversight. The UAB GCRC has the expertise in clinical coordination and data management necessary to perform the proposed clinical trials. The UAB-ACE Clinical Component includes expertise in autoimmune clinical trials from 6 specialties: Rheumatology; Endocrine/Transplantation; Hematology; Dermatology; Neurology; and Gastroenterology. Investigators in the UAB-ACE Clinical Component have outstanding track records in evaluation of novel therapeutic agents for autoimmune diseases as illustrated with the number of trials performed or underway and with publications in relevant diseases. The UAB ACE will bring together these clinical investigators to work across disciplinary lines to test new agents and develop new applications, while collaborating with the basic investigators to determine mechanisms of action. Two clinical trials are proposed. The first (PD: Carter) is a phase I trial in patients with systemic lupus erythematosus, to evaluate a novel, cytotoxic approach targeting Death Receptor 5 to selectively eliminate activated lymphocytes. The second (PD: Moreland) is a phase II trial evaluating IL-1 TRAP in patients with psoriatic arthritis, which illustrates the ability of UAB investigators to partner with the pharmaceutical industry to test new applications of translational agents. Proposed mechanistic studies by UAB investigators will test the concept of targeting only activated lymphocytes (Death Receptor 5) and investigate the role of IL-1 in psoriatic arthritis and the mechanisms of IL-1-driven inflammation and IL-1 signaling in inflammatory tissue (IL-1 TRAP). UAB has an outstanding record in testing of novel, translational therapies for autoimmune diseases. The UAB ACE Clinical Component is a multidisciplinary, collaborative program to unite these strengths to accelerate the testing of immunomodulatory therapies for autoimmune disease and to optimize the opportunity to use these trials to determine mechanisms of disease and treatment.